The goal of this application is to improve the understanding of bulbar (head) deterioration in Amyotrophic lateral sclerosis (ALS, also known as "Lou Gehrig's disease"), which is a fatal neurologic disease caused by degeneration of the motor neurons in the motor cortex, brainstem, and spinal cord. Despite the devastating consequences of bulbar deterioration, including impaired speech and swallowing, on the survival and quality of life of individuals with ALS, only a few studies have been conducted on ALS bulbar symptoms compared to research on ALS spinal involvement. This application responds to this gap in clinical and scientific knowledge by studying bulbar decline longitudinally and comprehensively using established and innovative methods for recording, measuring, and analyzing speech behaviors. One hundred persons with ALS will be studied every three months for a period of two years. The course of deterioration in each participant's speech will be tracked longitudinally using multiple measures of bulbar performance, with each measure broadly classified as either a representing speech performance at the global (i.e., speech system) level or subsystem level. The speech subsystem measures will represent the functional integrity of multiple bulbar regions known to support speech production, including the respiratory, phonatory, resonatory, and articulatory subsystems. Patterns of decline at each speech system and subsystem level will be used to address four specific aims: (1) determine if the rate of speech subsystem performance in the early stage of the disease accurately predicts the long-term rate of decline, (2) determine if speech subsystem measures accurately predict the onset of speech decline and the subsequent loss of oral communication, (3) identify sensitive quantitative indicators of the onset and rate of bulbar deterioration, and (4) identify several putative subtypes of bulbar ALS. In the short term, the identification of sensitive measures of bulbar involvement will improve early detection and prognostic accuracy and address the critical need for objective outcome measures in future experimental drug trials. The findings will also provide much needed information regarding the implications of speech subsystem deterioration on speech intelligibility. In the long term, the more refined endophenotype (i.e., hereditary characteristic) of bulbar involvement obtained from this research may strengthen future efforts at identifying the genetic loci of ALS and improving diagnostic and treatment specificity of the disease. PUBLIC HEALTH RELEVANCE: ALS, or Lou Gehrig's disease, is one of the most common and devastating neuromuscular diseases worldwide, affecting both women and men of all races and ethnic backgrounds. Loss of speech will eventually occur in most individuals with ALS whether the disease starts in the head/neck region or in the spine and is among the most debilitating outcomes of the disease. This research with ALS patients addresses three widely recognized needs in this population: early detection, improved prediction accuracy, and improved understanding of individual variation in the progression of the disease.